Transmembrane Protein TMEM230, a Target of Glioblastoma Therapy

Cinzia Cocola, Valerio Magnaghi, Edoardo Abeni, Paride Pelucchi, Valentina Martino, Laura Vilardo, Eleonora Piscitelli, Arianna Consiglio, Giorgio Grillo, Ettore Mosca, Roberta Gualtierotti, Daniela Mazzaccaro, Gina La Sala, Chiara Di Pietro, Mira Palizban, Sabino Liuni, Giuseppina DePedro, Stefano Morara, Giovanni Nano, James Kehler, Burkhard Greve, Alessio Noghero, Daniela Marazziti, Federico Bussolino, Gianfranco Bellipanni, Igea D'Agnano, Martin Götte, Ileana Zucchi, Rolland Reinbold, Cinzia Cocola, Valerio Magnaghi, Edoardo Abeni, Paride Pelucchi, Valentina Martino, Laura Vilardo, Eleonora Piscitelli, Arianna Consiglio, Giorgio Grillo, Ettore Mosca, Roberta Gualtierotti, Daniela Mazzaccaro, Gina La Sala, Chiara Di Pietro, Mira Palizban, Sabino Liuni, Giuseppina DePedro, Stefano Morara, Giovanni Nano, James Kehler, Burkhard Greve, Alessio Noghero, Daniela Marazziti, Federico Bussolino, Gianfranco Bellipanni, Igea D'Agnano, Martin Götte, Ileana Zucchi, Rolland Reinbold

Abstract

Glioblastomas (GBM) are the most aggressive tumors originating in the brain. Histopathologic features include circuitous, disorganized, and highly permeable blood vessels with intermittent blood flow. These features contribute to the inability to direct therapeutic agents to tumor cells. Known targets for anti-angiogenic therapies provide minimal or no effect in overall survival of 12-15 months following diagnosis. Identification of novel targets therefore remains an important goal for effective treatment of highly vascularized tumors such as GBM. We previously demonstrated in zebrafish that a balanced level of expression of the transmembrane protein TMEM230/C20ORF30 was required to maintain normal blood vessel structural integrity and promote proper vessel network formation. To investigate whether TMEM230 has a role in the pathogenesis of GBM, we analyzed its prognostic value in patient tumor gene expression datasets and performed cell functional analysis. TMEM230 was found necessary for growth of U87-MG cells, a model of human GBM. Downregulation of TMEM230 resulted in loss of U87 migration, substratum adhesion, and re-passaging capacity. Conditioned media from U87 expressing endogenous TMEM230 induced sprouting and tubule-like structure formation of HUVECs. Moreover, TMEM230 promoted vascular mimicry-like behavior of U87 cells. Gene expression analysis of 702 patients identified that TMEM230 expression levels distinguished high from low grade gliomas. Transcriptomic analysis of patients with gliomas revealed molecular pathways consistent with properties observed in U87 cell assays. Within low grade gliomas, elevated TMEM230 expression levels correlated with reduced overall survival independent from tumor subtype. Highest level of TMEM230 correlated with glioblastoma and ATP-dependent microtubule kinesin motor activity, providing a direction for future therapeutic intervention. Our studies support that TMEM230 has both glial tumor and endothelial cell intracellular and extracellular functions. Elevated levels of TMEM230 promote glial tumor cell migration, extracellular scaffold remodeling, and hypervascularization and abnormal formation of blood vessels. Downregulation of TMEM230 expression may inhibit both low grade glioma and glioblastoma tumor progression and promote normalization of abnormally formed blood vessels. TMEM230 therefore is both a promising anticancer and antiangiogenic therapeutic target for inhibiting GBM tumor cells and tumor-driven angiogenesis.

Keywords: angiogenesis and normalization of vascular network; anticancer and antiangiogenic therapy; cargo vesicle transport; glioma; kinesin motor proteins; tumor cell migration and adhesion.

Conflict of interest statement

IZ and RR have a patent accepted concerning the use of Agents that modulate TMEM230 in tumor associated angiogenesis. Patent Application International Publication number: 20200247882. Agents that modulate TMEM230 as angiogenesis regulators and that detect TMEM230 AS markers of metastasis. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Cocola, Magnaghi, Abeni, Pelucchi, Martino, Vilardo, Piscitelli, Consiglio, Grillo, Mosca, Gualtierotti, Mazzaccaro, La Sala, Di Pietro, Palizban, Liuni, DePedro, Morara, Nano, Kehler, Greve, Noghero, Marazziti, Bussolino, Bellipanni, D’Agnano, Götte, Zucchi and Reinbold.

Figures

FIGURE 1
FIGURE 1
Expression of TMEM230 in brain Glioblastoma Multiforme (GBM) and Low-Grade Gliomas (LGG) analyzed from The Cancer Genome Atlas. (A) Glioblastoma multiforme tumors showed significantly elevated level of TMEM230 mRNA compared to low-grade gliomas (unpaired t-test p < 0.0001). Low-grade gliomas consist of astrocytoma, oligoastrocytoma and oligodendroglioma patient samples. (B) Poor prognosis was correlated with high TMEM230 in low-grade gliomas. (C) Poor prognosis was correlated with high TMEM230 in astrocytoma (top), oligoastrocytoma (middle) and oligodendroglioma (bottom). Relationship between TMEM230 expression levels and prognosis of low-grade gliomas affected patients indicated that lower expression of TMEM230 was associated with increased overall survival. Each glioma subtype is indicated by the median of gene expression of TMEM230. B and C analyses were generated from the Kaplan-Meier test based on the expression of medium TMEM230.(D) Representative heatmap displaying the most variable expressed genes for astrocytoma using the R with “pheatmap” package for which functional enrichment was generated with DAVID program.
FIGURE 2
FIGURE 2
Validation of endogenous and lentivirus downregulation of TMEM230 mRNA and protein expression in U87-MG cells. (A) Validation of constitutive downregulation of endogenous TMEM230 transcript expression with lentiviral system. Endogenous control: HPRT, Error bars represent 95% confidence interval. (B) Validation of constitutive downregulation of endogenous TMEM230 protein expression with the lentiviral system. Endogenous control: β-actin. (C) Western blot analysis (top panel) showed TMEM230 protein was not detected in fetal bovine serum (FBS), serum replacement (SR) or conditioned media (CM) containing serum replacement or FBS (CM SR and CM FBS) obtained from endogenous TMEM230 expressing U87 cells. Ponceau S staining (lower panel) showed an abundance of protein was loaded. (D) Coomassie blue staining showed an increase of expression of extracellular vesicle membrane protein, CD81 in conditioned media of U87 cells constitutively over-expressing TMEM230 with respect to conditioned media collected from control cells (U87GFP and U87shSCR). Detection of CD81 (D) but lack of detection of TMEM230 protein in culture media (C) supports that the TMEM230 protein regulates extracellular vesicle generation or secretion but is not itself a component of extracellular vesicles.
FIGURE 3
FIGURE 3
Downregulation of TMEM230 was sufficient to promote loss of U87-MG substratum adhesion capacity in fetal bovine serum containing media. Control (U87shSCR) and U87 cells in which TMEM230 was constitutively downregulated (U87shTMEM230) were cultured in extracellular vesicle depleted FBS (Fetal Bovine Serum) containing culture media. Equal number of control cells and cells in which endogenous TMEM230 was downregulated were plated (P0) in vesicle depleted FBS containing culture media and monitored over 72 h, starting from when green fluorescent protein (GFP) expression was first observed (0 h, not shown). Cells in which TMEM230 were downregulated displayed decrease in cytoplasm dimensions and disrupted cytoplasmic invadopodium like extensions. Cells were re-passaged (P1) and monitored for additional 144 h. Re-passaged cells (P1) displayed a more limited capacity for cell adhesion, supporting that TMEM230 is necessary for scaffold attachment of cells.
FIGURE 4
FIGURE 4
Downregulation of endogenous TMEM230 was sufficient to promote loss of U87-MG substratum adhesion capacity in serum replacement containing media. Control (U87shSCR) and U87 cells in which TMEM230 was constitutively downregulated (U87shTMEM230) were cultured in serum replacement (SR) containing media (P0). Equal number of control cells and cells in which TMEM230 was downregulated were plated in SR containing culture media and monitored over 192 h, starting from when GFP expression was first observed (0 h).
FIGURE 5
FIGURE 5
Human umbilical vein endothelial cells cultured in FBS and serum replacement containing conditioned media from U87-MG cells expressing endogenous TMEM230 promoted angiogenic behavior. (1–4) Representative images at 24 h of human umbilical vein endothelial cells (HUVEC) in Matrigel treated with conditioned media obtained from 3 days cultures of U87 control (U87shSCR) and U87 in which TMEM230 was down regulated (U87shTMEM230). (5–15) Human umbilical vein endothelial cells in 3D treated with conditioned media obtained from 3 days cultures of U87 control and U87 which TMEM230 was down regulated shown for without (5–9) and with angiogenic factors (11–14). U87 cells were cultured in media containing fetal bovine serum (FBS) or serum replacement (SR).
FIGURE 6
FIGURE 6
Endogenous TMEM230 promoted U87-MG cell migration, tumor-endothelial cell contact and displacement in co-culture assays. (A) Low magnification shows the co-culture assay set up. (B) Representative images showing the periphery (outgrowth) and core (initial location of cell plating) of U87shTMEM230 cells at 48 h. Downregulation of TMEM230 in U87 cells was associated with cytoplasm of reduced mass, disrupted cytoplasmic invadopodium like extensions, decreased cell anchorage and reduced contacts among initially confluent plated cells. (C) Representative images of U87shTMEM230 cells at periphery and core at 9 days. U87 cells with reduced TMEM230 expression displayed reduced anchorage capacity and motility (see red circle at periphery of initial site of plating of the confluent cells) compared to control cells. (D–F) Displacement of the confluent human umbilical vein endothelial cells by U87 control cells (U87shSCR) expressing endogenous TMEM230 through infiltration into the confluent mass of human umbilical vein endothelial cells (see red circles), a behavior that is associated with the first step of intussusceptive induced blood vessel branching.
FIGURE 7
FIGURE 7
Endogenous expression of TMEM230 promoted U87-MG migration and tubule like structure formation recapitulating a vascular mimicry like behavior. (A) Representative 3D bodies or structures (only the borders of a larger 3D body of U87shSCR or a complete body of U87shTMEM230 cells are shown by red circles) of U87 cells expressing endogenous TMEM230 displayed vascular mimicry, cell sprouting, collective cell movement, and invasion in 3D Matrigel. U87 cells in which endogenous TMEM230 was downregulated did not generate 3D bodies of significant size in agreement that TMEM230 was required for U87 cell growth. Two different media were used for generating VM like structures from U87 cells, media used for culturing adherent U87 tumor cells or HUVEC shown in Figures 3, 5 (top panel), respectively. (B) Higher magnification of control cells.
FIGURE 8
FIGURE 8
All enriched pathways identified with high or low TMEM230 expression in diverse patient glioma tumors. (A) Enriched pathways identified common between high or low TMEM230 expression in all LGG of patient. (B) Scheme for identifying different pathways between high or low TMEM230 expression in LGG and glioblastomas. (C) Enriched pathways identified different between high or low TMEM230 expression in LGG and glioblastoma. See corresponding Supplementary Table 12.

References

    1. Achen M. G., Stacker S. A. (1998). The vascular endothelial growth factor family; proteins which guide the development of the vasculature. Int. J. Exp. Pathol. 79 255–265.
    1. Ahir B. K., Engelhard H. H., Lakka S. S. (2020). Tumor Development and Angiogenesis in Adult Brain Tumor: glioblastoma. Mol. Neurobiol. 57 2461–2478. 10.1007/s12035-020-01892-8
    1. Ahsan R., Baisiwala S., Ahmed A. U. (2017). Rogue one: another faction of the Wnt empire implicated in assisting GBM progression. Transl. Cancer Res. 6 S321–S327. 10.21037/tcr.2017.03.29
    1. Aldape K., Zadeh G., Mansouri S., Reifenberger G., Von Deimling A. (2015). Glioblastoma: pathology, molecular mechanisms and markers. Acta Neuropathol. 129 829–848.
    1. Ali I., Yang W. C. (2020). The functions of kinesin and kinesin-related proteins in eukaryotes. Cell Adh. Migr. 14 139–152.
    1. Alves T. R., Lima F. R., Kahn S. A., Lobo D., Dubois L. G., Soletti R., et al. (2011). Glioblastoma cells: a heterogeneous and fatal tumor interacting with the parenchyma. Life Sci. 89 532–539. 10.1016/j.lfs.2011.04.022
    1. Ameratunga M., Pavlakis N., Wheeler H., Grant R., Simes J., Khasraw M. (2018). Anti-angiogenic therapy for high-grade glioma. Cochrane Database Syst. Rev. 11:CD008218.
    1. Angara K., Borin T. F., Arbab A. S. (2017). Vascular Mimicry: a Novel Neovascularization Mechanism Driving Anti-Angiogenic Therapy (AAT) Resistance in Glioblastoma. Transl. Oncol. 10 650–660. 10.1016/j.tranon.2017.04.007
    1. Angelopoulou E., Piperi C. (2018). Emerging role of plexins signaling in glioma progression and therapy. Cancer Lett. 414 81–87. 10.1016/j.canlet.2017.11.010
    1. Anthony C., Mladkova-Suchy N., Adamson D. C. (2019). The evolving role of antiangiogenic therapies in glioblastoma multiforme: current clinical significance and future potential. Expert Opin. Investig. Drugs 28 787–797. 10.1080/13543784.2019.1650019
    1. Arbab A. S., Jain M., Achyut B. R. (2015). Vascular Mimicry: the Next Big Glioblastoma Target. Biochem. Physiol. 4:e410. 10.4172/2168-9652.1000e140
    1. Argyriou A. A., Giannopoulou E., Kalofonos H. P. (2009). Angiogenesis and anti-angiogenic molecularly targeted therapies in malignant gliomas. Oncology 77 1–11. 10.1159/000218165
    1. Armento A., Ehlers J., Schotterl S., Naumann U. (2017). “Molecular Mechanisms of Glioma Cell Motility,” in Glioblastoma, ed. De Vleeschouwer S. (Brisbane (AU)): Codon Publications; ).
    1. Arrillaga-Romany I., Norden A. D. (2014). Antiangiogenic therapies for glioblastoma. CNS Oncol. 3 349–358. 10.2217/cns.14.31
    1. Axnick J., Lammert E. (2012). Vascular lumen formation. Curr. Opin. Hematol. 19 192–198. 10.1097/moh.0b013e3283523ebc
    1. Balkwill F. (2003). Chemokine biology in cancer. Semin. Immunol. 15 49–55. 10.1016/s1044-5323(02)00127-6
    1. Bartolotti M., Franceschi E., Poggi R., Tosoni A., Di Battista M., Brandes A. A. (2014). Resistance to antiangiogenic therapies. Future Oncol. 10 1417–1425.
    1. Batiuk M. Y., De Vin F., Duque S. I., Li C., Saito T., Saido T., et al. (2017). An immunoaffinity-based method for isolating ultrapure adult astrocytes based on ATP1B2 targeting by the ACSA-2 antibody. J. Biol. Chem. 292 8874–8891. 10.1074/jbc.M116.765313
    1. Batiuk M. Y., Martirosyan A., Wahis J., De Vin F., Marneffe C., Kusserow C., et al. (2020). Identification of region-specific astrocyte subtypes at single cell resolution. Nat. Commun. 11:1220. 10.1038/s41467-019-14198-8
    1. Bayraktar O. A., Bartels T., Holmqvist S., Kleshchevnikov V., Martirosyan A., Polioudakis D., et al. (2020). Astrocyte layers in the mammalian cerebral cortex revealed by a single-cell in situ transcriptomic map. Nat. Neurosci. 23 500–509. 10.1038/s41593-020-0602-1
    1. Bello L., Giussani C., Carrabba G., Pluderi M., Costa F., Bikfalvi A. (2004). Angiogenesis and invasion in gliomas. Cancer Treat. Res. 117 263–284. 10.1007/978-1-4419-8871-3_16
    1. Belotti D., Foglieni C., Resovi A., Giavazzi R., Taraboletti G. (2011). Targeting angiogenesis with compounds from the extracellular matrix. Int. J. Biochem. Cell Biol. 43 1674–1685. 10.1016/j.biocel.2011.08.012
    1. Bergers G., Hanahan D. (2008). Modes of resistance to anti-angiogenic therapy. Nat. Rev. Cancer 8 592–603. 10.1038/nrc2442
    1. Birk H. S., Han S. J., Butowski N. A. (2017). Treatment options for recurrent high-grade gliomas. CNS Oncol. 6 61–70. 10.2217/cns-2016-0013
    1. Bissell M. J. (1999). Tumor plasticity allows vasculogenic mimicry, a novel form of angiogenic switch. A rose by any other name? Am. J. Pathol. 155 675–679. 10.1016/S0002-9440(10)65164-4
    1. Box C., Rogers S. J., Mendiola M., Eccles S. A. (2010). Tumour-microenvironmental interactions: paths to progression and targets for treatment. Semin. Cancer Biol. 20 128–138. 10.1016/j.semcancer.2010.06.004
    1. Brandes A. A., Tosoni A., Franceschi E., Reni M., Gatta G., Vecht C. (2008). Glioblastoma in adults. Crit. Rev. Oncol. Hematol. 67 139–152.
    1. Brooks S. A., Lomax-Browne H. J., Carter T. M., Kinch C. E., Hall D. M. (2010). Molecular interactions in cancer cell metastasis. Acta Histochem. 112 3–25.
    1. Brown P. D., Giavazzi R. (1995). Matrix metalloproteinase inhibition: a review of anti-tumour activity. Ann. Oncol. 6 967–974.
    1. Bugyik E., Renyi-Vamos F., Szabo V., Dezso K., Ecker N., Rokusz A., et al. (2016). Mechanisms of vascularization in murine models of primary and metastatic tumor growth. Chin. J. Cancer 35:19.
    1. Burri P. H., Hlushchuk R., Djonov V. (2004). Intussusceptive angiogenesis: its emergence, its characteristics, and its significance. Dev. Dyn. 231 474–488. 10.1002/dvdy.20184
    1. Caby M. P., Lankar D., Vincendeau-Scherrer C., Raposo G., Bonnerot C. (2005). Exosomal-like vesicles are present in human blood plasma. Int. Immunol. 17 879–887.
    1. Cancer Genome Atlas Research Network, Weinstein J. N., Collisson E. A., Mills G. B., Shaw K. R., Ozenberger B. A., et al. (2013). The Cancer Genome Atlas Pan-Cancer analysis project. Nat. Genet. 45 1113–1120.
    1. Carra S., Sangiorgio L., Pelucchi P., Cermenati S., Mezzelani A., Martino V., et al. (2018). Zebrafish Tmem230a cooperates with the Delta/Notch signaling pathway to modulate endothelial cell number in angiogenic vessels. J. Cell. Physiol. 233 1455–1467. 10.1002/jcp.26032
    1. Catalano V., Turdo A., Di Franco S., Dieli F., Todaro M., Stassi G. (2013). Tumor and its microenvironment: a synergistic interplay. Semin. Cancer Biol. 23 522–532. 10.1016/j.semcancer.2013.08.007
    1. Ceci C., Atzori M. G., Lacal P. M., Graziani G. (2020). Role of VEGFs/VEGFR-1 Signaling and its Inhibition in Modulating Tumor Invasion: experimental Evidence in Different Metastatic Cancer Models. Int. J. Mol. Sci. 21:1388. 10.3390/ijms21041388
    1. Chintala S. K., Tonn J. C., Rao J. S. (1999). Matrix metalloproteinases and their biological function in human gliomas. Int. J. Dev. Neurosci. 17 495–502.
    1. Chowdhary S., Chamberlain M. (2013). Bevacizumab for the treatment of glioblastoma. Expert Rev. Neurother. 13 937–949.
    1. Conedera S. A., Li Y., Funayama M., Yoshino H., Nishioka K., Hattori N. (2018). Genetic analysis of TMEM230 in Japanese patients with familial Parkinson’s disease. Parkinsonism Relat. Disord. 48 107–108. 10.1016/j.parkreldis.2017.12.020
    1. Crampton S. P., Davis J., Hughes C. C. (2007). Isolation of human umbilical vein endothelial cells (HUVEC). J. Vis. Exp. 2007:183.
    1. Crawford Y., Ferrara N. (2009). VEGF inhibition: insights from preclinical and clinical studies. Cell Tissue Res. 335 261–269. 10.1007/s00441-008-0675-8
    1. Curry R. C., Dahiya S., Alva Venur V., Raizer J. J., Ahluwalia M. S. (2015). Bevacizumab in high-grade gliomas: past, present, and future. Expert Rev. Anticancer Ther. 15 387–397. 10.1586/14737140.2015.1028376
    1. Darmanis S., Sloan S. A., Croote D., Mignardi M., Chernikova S., Samghababi P., et al. (2017). Single-Cell RNA-Seq Analysis of Infiltrating Neoplastic Cells at the Migrating Front of Human Glioblastoma. Cell Rep. 21 1399–1410. 10.1016/j.celrep.2017.10.030
    1. Darmanis S., Sloan S. A., Zhang Y., Enge M., Caneda C., Shuer L. M., et al. (2015). A survey of human brain transcriptome diversity at the single cell level. Proc. Natl. Acad. Sci. U. S. A. 112 7285–7290. 10.1073/pnas.1507125112
    1. de Groot J., Reardon D. A., Batchelor T. T. (2013). Antiangiogenic therapy for glioblastoma: the challenge of translating response rate into efficacy. Am. Soc. Clin. Oncol. Educ. Book 33. 10.1200/EdBook_AM.2013.33.e71
    1. De Spiegelaere W., Casteleyn C., Van Den Broeck W., Plendl J., Bahramsoltani M., Simoens P., et al. (2012). Intussusceptive angiogenesis: a biologically relevant form of angiogenesis. J. Vasc. Res. 49 390–404. 10.1159/000338278
    1. Deng H., Fan K., Jankovic J. (2018). The Role of TMEM230 Gene in Parkinson’s Disease. J. Parkinsons Dis. 8 469–477.
    1. Deng H. X., Shi Y., Yang Y., Ahmeti K. B., Miller N., Huang C., et al. (2016). Identification of TMEM230 mutations in familial Parkinson’s disease. Nat. Genet. 48 733–739. 10.1038/ng.3589
    1. Diaz-Flores L., Gutierrez R., Gayoso S., Garcia M. P., Gonzalez-Gomez M., Diaz-Flores L., Jr., et al. (2020). Intussusceptive angiogenesis and its counterpart intussusceptive lymphangiogenesis. Histol. Histopathol. 35 1083–1103. 10.14670/HH-18-222
    1. Djonov V., Baum O., Burri P. H. (2003). Vascular remodeling by intussusceptive angiogenesis. Cell Tissue Res. 314 107–117. 10.1007/s00441-003-0784-3
    1. Djonov V., Makanya A. N. (2005). New insights into intussusceptive angiogenesis. EXS 94 17–33.
    1. Dome B., Hendrix M. J., Paku S., Tovari J., Timar J. (2007). Alternative vascularization mechanisms in cancer: pathology and therapeutic implications. Am. J. Pathol. 170 1–15. 10.2353/ajpath.2007.060302
    1. Fathi Maroufi N., Taefehshokr S., Rashidi M. R., Taefehshokr N., Khoshakhlagh M., Isazadeh A., et al. (2020). Vascular mimicry: changing the therapeutic paradigms in cancer. Mol. Biol. Rep. 47 4749–4765. 10.1007/s11033-020-05515-2
    1. Feiguin F., Ferreira A., Kosik K. S., Caceres A. (1994). Kinesin-mediated organelle translocation revealed by specific cellular manipulations. J. Cell Biol. 127 1021–1039. 10.1083/jcb.127.4.1021
    1. Fischer I., Gagner J. P., Law M., Newcomb E. W., Zagzag D. (2005). Angiogenesis in gliomas: biology and molecular pathophysiology. Brain Pathol. 15 297–310. 10.1111/j.1750-3639.2005.tb00115.x
    1. Funakoshi Y., Hata N., Kuga D., Hatae R., Sangatsuda Y., Fujioka Y., et al. (2020). Update on Chemotherapeutic Approaches and Management of Bevacizumab Usage for Glioblastoma. Pharmaceuticals 13:470. 10.3390/ph13120470
    1. Furnish M., Caino M. C. (2020). Altered mitochondrial trafficking as a novel mechanism of cancer metastasis. Cancer Rep. 3:e1157. 10.1002/cnr2.1157
    1. Gately L., Mclachlan S. A., Philip J., Rathi V., Dowling A. (2019). Molecular profile of long-term survivors of glioblastoma: a scoping review of the literature. J. Clin. Neurosci. 68 1–8. 10.1016/j.jocn.2019.08.017
    1. Ge H., Luo H. (2018). Overview of advances in vasculogenic mimicry - a potential target for tumor therapy. Cancer Manag. Res. 10 2429–2437. 10.2147/CMAR.S164675
    1. Ghiaseddin A., Peters K. B. (2015). Use of bevacizumab in recurrent glioblastoma. CNS Oncol. 4 157–169. 10.2217/cns.15.8
    1. Groblewska M., Litman-Zawadzka A., Mroczko B. (2020). The Role of Selected Chemokines and Their Receptors in the Development of Gliomas. Int. J. Mol. Sci. 21:3704. 10.3390/ijms21103704
    1. Guida P., Piscitelli E., Marrese M., Martino V., Cirillo V., Guarino V., et al. (2020). Integrating Microstructured Electrospun Scaffolds in an Open Microfluidic System for in Vitro Studies of Human Patient-Derived Primary Cells. ACS Biomater. Sci. Eng. 6 3649–3663. 10.1021/acsbiomaterials.0c00352
    1. Gusyatiner O., Hegi M. E. (2018). Glioma epigenetics: from subclassification to novel treatment options. Semin. Cancer Biol. 51 50–58. 10.1016/j.semcancer.2017.11.010
    1. Haqqani A. S., Delaney C. E., Tremblay T. L., Sodja C., Sandhu J. K., Stanimirovic D. B. (2013). Method for isolation and molecular characterization of extracellular microvesicles released from brain endothelial cells. Fluids Barriers CNS 10:4. 10.1186/2045-8118-10-4
    1. Hehnly H., Stamnes M. (2007). Regulating cytoskeleton-based vesicle motility. FEBS Lett. 581 2112–2118. 10.1016/j.febslet.2007.01.094
    1. Heiss M., Hellstrom M., Kalen M., May T., Weber H., Hecker M., et al. (2015). Endothelial cell spheroids as a versatile tool to study angiogenesis in vitro. FASEB J. 29 3076–3084. 10.1096/fj.14-267633
    1. Hielscher A. C., Gerecht S. (2012). Engineering approaches for investigating tumor angiogenesis: exploiting the role of the extracellular matrix. Cancer Res. 72 6089–6096. 10.1158/0008-5472.CAN-12-2773
    1. Hillen F., Griffioen A. W. (2007). Tumour vascularization: sprouting angiogenesis and beyond. Cancer Metastasis Rev. 26 489–502.
    1. Hlushchuk R., Makanya A. N., Djonov V. (2011). Escape mechanisms after antiangiogenic treatment, or why are the tumors growing again? Int. J. Dev. Biol. 55 563–567. 10.1387/ijdb.103231rh
    1. Huang da W., Sherman B. T., Lempicki R. A. (2009). Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protoc. 4 44–57.
    1. Jain R. K. (2013). Normalizing tumor microenvironment to treat cancer: bench to bedside to biomarkers. J. Clin. Oncol. 31 2205–2218. 10.1200/jco.2012.46.3653
    1. Jeppesen D. K., Hvam M. L., Primdahl-Bengtson B., Boysen A. T., Whitehead B., Dyrskjot L., et al. (2014). Comparative analysis of discrete exosome fractions obtained by differential centrifugation. J. Extracell. Vesicles 3:25011. 10.3402/jev.v3.25011
    1. Jo J., Schiff D., Purow B. (2012). Angiogenic inhibition in high-grade gliomas: past, present and future. Expert Rev. Neurother. 12 733–747. 10.1586/ern.12.53
    1. Jo J., Wen P. Y. (2018). Antiangiogenic Therapy of High-Grade Gliomas. Prog. Neurol. Surg. 31 180–199.
    1. Jones J., Nguyen H., Drummond K., Morokoff A. (2021). Circulating Biomarkers for Glioma: a Review. Neurosurgery 88 E221–E230.
    1. Jovcevska I. (2018). Sequencing the next generation of glioblastomas. Crit. Rev. Clin. Lab. Sci. 55 264–282.
    1. Kang X., Zheng Y., Hong W., Chen X., Li H., Huang B., et al. (2020). Recent Advances in Immune Cell Therapy for Glioblastoma. Front. Immunol. 11:544563. 10.3389/fimmu.2020.544563
    1. Karpati G., Li H., Nalbantoglu J. (1999). Molecular therapy for glioblastoma. Curr. Opin. Mol. Ther. 1 545–552.
    1. Kim M. J., Deng H. X., Wong Y. C., Siddique T., Krainc D. (2017). The Parkinson’s disease-linked protein TMEM230 is required for Rab8a-mediated secretory vesicle trafficking and retromer trafficking. Hum. Mol. Genet. 26 729–741. 10.1093/hmg/ddw413
    1. Kondo Y., Katsushima K., Ohka F., Natsume A., Shinjo K. (2014). Epigenetic dysregulation in glioma. Cancer Sci. 105 363–369.
    1. Konjikusic M. J., Gray R. S., Wallingford J. B. (2021). The developmental biology of kinesins. Dev. Biol. 469 26–36.
    1. Krishna Priya S., Nagare R. P., Sneha V. S., Sidhanth C., Bindhya S., Manasa P., et al. (2016). Tumour angiogenesis-Origin of blood vessels. Int. J. Cancer 139 729–735. 10.1002/ijc.30067
    1. Langford G. M. (1995). Actin- and microtubule-dependent organelle motors: interrelationships between the two motility systems. Curr. Opin. Cell Biol. 7 82–88. 10.1016/0955-0674(95)80048-4
    1. Lechertier T., Hodivala-Dilke K. (2012). Focal adhesion kinase and tumour angiogenesis. J. Pathol. 226 404–412.
    1. Lefranc F., Le Rhun E., Kiss R., Weller M. (2018). Glioblastoma quo vadis: will migration and invasiveness reemerge as therapeutic targets? Cancer Treat. Rev. 68 145–154. 10.1016/j.ctrv.2018.06.017
    1. Levin E. G. (2005). Cancer therapy through control of cell migration. Curr. Cancer Drug Targets 5 505–518. 10.2174/156800905774574048
    1. Li B., Dewey C. N. (2011). RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinformatics 12:323. 10.1186/1471-2105-12-323
    1. Lopes Abath Neto O., Aldape K. (2021). Morphologic and Molecular Aspects of Glioblastomas. Neurosurg. Clin. N. Am. 32 149–158.
    1. Love M. I., Huber W., Anders S. (2014). Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15:550. 10.1186/s13059-014-0550-8
    1. Ludwig K., Kornblum H. I. (2017). Molecular markers in glioma. J. Neurooncol. 134 505–512.
    1. Mackay C. R. (2008). Moving targets: cell migration inhibitors as new anti-inflammatory therapies. Nat. Immunol. 9 988–998. 10.1038/ni.f.210
    1. Majidpoor J., Mortezaee K. (2021). Angiogenesis as a hallmark of solid tumors - clinical perspectives. Cell. Oncol. 44 715–737. 10.1007/s13402-021-00602-3
    1. Makanya A. N., Hlushchuk R., Djonov V. G. (2009). Intussusceptive angiogenesis and its role in vascular morphogenesis, patterning, and remodeling. Angiogenesis 12 113–123. 10.1007/s10456-009-9129-5
    1. Mandemakers W., Quadri M., Stamelou M., Bonifati V. (2017). TMEM230: how does it fit in the etiology and pathogenesis of Parkinson’s disease? Mov. Disord. 32 1159–1162. 10.1002/mds.27061
    1. Masui K., Mischel P. S., Reifenberger G. (2016). Molecular classification of gliomas. Handb. Clin. Neurol. 134 97–120. 10.1016/b978-0-12-802997-8.00006-2
    1. Mei X., Chen Y. S., Zhang Q. P., Chen F. R., Xi S. Y., Long Y. K., et al. (2020). Association between glioblastoma cell-derived vessels and poor prognosis of the patients. Cancer Commun. 40 211–221. 10.1002/cac2.12026
    1. Mentzer S. J., Konerding M. A. (2014). Intussusceptive angiogenesis: expansion and remodeling of microvascular networks. Angiogenesis 17 499–509. 10.1007/s10456-014-9428-3
    1. Montano N., D’alessandris Q. G., Izzo A., Fernandez E., Pallini R. (2016). Biomarkers for glioblastoma multiforme: status quo. J. Clin. Transl. Res. 2 3–10.
    1. Nagarajan R. P., Costello J. F. (2009). Epigenetic mechanisms in glioblastoma multiforme. Semin. Cancer Biol. 19 188–197.
    1. Nakatsu M. N., Hughes C. C. (2008). An optimized three-dimensional in vitro model for the analysis of angiogenesis. Methods Enzymol. 443 65–82.
    1. Nakatsu M. N., Sainson R. C., Aoto J. N., Taylor K. L., Aitkenhead M., Perez-Del-Pulgar S., et al. (2003). Angiogenic sprouting and capillary lumen formation modeled by human umbilical vein endothelial cells (HUVEC) in fibrin gels: the role of fibroblasts and Angiopoietin-1. Microvasc. Res. 66 102–112. 10.1016/s0026-2862(03)00045-1
    1. Nowak-Sliwinska P., Alitalo K., Allen E., Anisimov A., Aplin A. C., Auerbach R., et al. (2018). Consensus guidelines for the use and interpretation of angiogenesis assays. Angiogenesis 21 425–532.
    1. Ohgaki H., Kleihues P. (2005). Epidemiology and etiology of gliomas. Acta Neuropathol. 109 93–108.
    1. Oosawa F. (1995). Sliding and ATPase. J. Biochem. 118 863–870. 10.1093/jb/118.5.863
    1. Polivka J., Jr., Polivka J., Holubec L., Kubikova T., Priban V., Hes O., et al. (2017). Advances in Experimental Targeted Therapy and Immunotherapy for Patients with Glioblastoma Multiforme. Anticancer Res. 37 21–33.
    1. Pozzi A., Zent R. (2009). Regulation of endothelial cell functions by basement membrane- and arachidonic acid-derived products. Wiley Interdiscip. Rev. Syst. Biol. Med. 1 254–272. 10.1002/wsbm.7
    1. Puzzilli F., Ruggeri A., Mastronardi L., Di Stefano D., Lunardi P. (1998). Long-term survival in cerebral glioblastoma. Case report and critical review of the literature. Tumori 84 69–74.
    1. Redzic J. S., Ung T. H., Graner M. W. (2014). Glioblastoma extracellular vesicles: reservoirs of potential biomarkers. Pharmgenomics Pers. Med. 7 65–77.
    1. Ribatti D., Crivellato E. (2012). “Sprouting angiogenesis”, a reappraisal. Dev. Biol. 372 157–165. 10.1016/j.ydbio.2012.09.018
    1. Ribatti D., Djonov V. (2012). Intussusceptive microvascular growth in tumors. Cancer Lett. 316 126–131. 10.1016/j.canlet.2011.10.040
    1. Ribatti D., Pezzella F. (2021). Overview on the Different Patterns of Tumor Vascularization. Cells 10:639. 10.3390/cells10030639
    1. Romani M., Pistillo M. P., Banelli B. (2018). Epigenetic Targeting of Glioblastoma. Front. Oncol. 8:448. 10.3389/fonc.2018.00448
    1. Sacewicz I., Wiktorska M., Wysocki T., Niewiarowska J. (2009). [Mechanisms of cancer angiogenesis]. Postepy Hig. Med. Dosw. 63 159–168.
    1. Saravanan S., Vimalraj S., Pavani K., Nikarika R., Sumantran V. N. (2020). Intussusceptive angiogenesis as a key therapeutic target for cancer therapy. Life Sci. 252:117670. 10.1016/j.lfs.2020.117670
    1. Simon-Assmann P., Orend G., Mammadova-Bach E., Spenle C., Lefebvre O. (2011). Role of laminins in physiological and pathological angiogenesis. Int. J. Dev. Biol. 55 455–465. 10.1387/ijdb.103223ps
    1. Sogno I., Vene R., Sapienza C., Ferrari N., Tosetti F., Albini A. (2009). Anti-angiogenic properties of chemopreventive drugs: fenretinide as a prototype. Recent Results Cancer Res. 181 71–76. 10.1007/978-3-540-69297-3_8
    1. Tate M. C., Aghi M. K. (2009). Biology of angiogenesis and invasion asion in glioma. Neurotherapeutics 6 447–457.
    1. Thomas A. A., Brennan C. W., Deangelis L. M., Omuro A. M. (2014). Emerging therapies for glioblastoma. JAMA Neurol. 71 1437–1444. 10.1001/jamaneurol.2014.1701
    1. Touat M., Idbaih A., Sanson M., Ligon K. L. (2017). Glioblastoma targeted therapy: updated approaches from recent biological insights. Ann. Oncol. 28 1457–1472. 10.1093/annonc/mdx106
    1. Treps L., Faure S., Clere N. (2021). Vasculogenic mimicry, a complex and devious process favoring tumorigenesis - Interest in making it a therapeutic target. Pharmacol. Ther. 223:107805. 10.1016/j.pharmthera.2021.107805
    1. Trevisan E., Bertero L., Bosa C., Magistrello M., Pellerino A., Ruda R., et al. (2014). Antiangiogenic therapy of brain tumors: the role of bevacizumab. Neurol. Sci. 35 507–514.
    1. Uddin M. S., Mamun A. A., Alghamdi B. S., Tewari D., Jeandet P., Sarwar M. S., et al. (2020). Epigenetics of glioblastoma multiforme: from molecular mechanisms to therapeutic approaches. Semin. Cancer Biol. [Epub Online ahead of print]. 10.1016/j.semcancer.2020.12.015
    1. Ushio Y. (1991). Treatment of gliomas in adults. Curr. Opin. Oncol. 3 467–475.
    1. Vartanian A., Singh S. K., Agnihotri S., Jalali S., Burrell K., Aldape K. D., et al. (2014). GBM’s multifaceted landscape: highlighting regional and microenvironmental heterogeneity. Neuro Oncol. 16 1167–1175. 10.1093/neuonc/nou035
    1. Visted T., Enger P. O., Lund-Johansen M., Bjerkvig R. (2003). Mechanisms of tumor cell invasion and angiogenesis in the central nervous system. Front. Biosci. 8:e289–e304. 10.2741/1026
    1. Wan Y. W., Allen G. I., Liu Z. (2016). TCGA2STAT: simple TCGA data access for integrated statistical analysis in R. Bioinformatics 32 952–954. 10.1093/bioinformatics/btv677
    1. Wang X., Whelan E., Liu Z., Liu C. F., Smith W. W. (2021). Controversy of TMEM230 Associated with Parkinson’s Disease. Neuroscience 453 280–286. 10.1016/j.neuroscience.2020.11.004
    1. Wang Y., Xing D., Zhao M., Wang J., Yang Y. (2016). The Role of a Single Angiogenesis Inhibitor in the Treatment of Recurrent Glioblastoma Multiforme: a Meta-Analysis and Systematic Review. PLoS One 11:e0152170. 10.1371/journal.pone.0152170
    1. Weathers S. P., De Groot J. (2014). Resistance to antiangiogenic therapy. Curr. Neurol. Neurosci. Rep. 14:443.
    1. Weathers S. P., De Groot J. (2015). VEGF Manipulation in Glioblastoma. Oncology 29 720–727.
    1. Wechman S. L., Emdad L., Sarkar D., Das S. K., Fisher P. B. (2020). Vascular mimicry: triggers, molecular interactions and in vivo models. Adv. Cancer Res. 148 27–67. 10.1016/bs.acr.2020.06.001
    1. Wei X., Chen Y., Jiang X., Peng M., Liu Y., Mo Y., et al. (2021). Mechanisms of vasculogenic mimicry in hypoxic tumor microenvironments. Mol. Cancer 20:7.
    1. Widodo S. S., Hutchinson R. A., Fang Y., Mangiola S., Neeson P. J., Darcy P. K., et al. (2021). Toward precision immunotherapy using multiplex immunohistochemistry and in silico methods to define the tumor immune microenvironment. Cancer Immunol. Immunother. 70 1811–1820. 10.1007/s00262-020-02801-7
    1. Wirsching H. G., Galanis E., Weller M. (2016). Glioblastoma. Handb. Clin. Neurol. 134 381–397.
    1. Xu R., Pisapia D., Greenfield J. P. (2016). Malignant Transformation in Glioma Steered by an Angiogenic Switch: defining a Role for Bone Marrow-Derived Cells. Cureus 8:e471. 10.7759/cureus.471
    1. Zavyalova M. V., Denisov E. V., Tashireva L. A., Savelieva O. E., Kaigorodova E. V., Krakhmal N. V., et al. (2019). Intravasation as a Key Step in Cancer Metastasis. Biochemistry 84 762–772. 10.1134/s0006297919070071
    1. Zhang Y., Wang S., Dudley A. C. (2020). Models and molecular mechanisms of blood vessel co-option by cancer cells. Angiogenesis 23 17–25. 10.1007/s10456-019-09684-y
    1. Zhou Y., Wu W., Bi H., Yang D., Zhang C. (2020). Glioblastoma precision therapy: from the bench to the clinic. Cancer Lett. 475 79–91. 10.1016/j.canlet.2020.01.027

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